The transition to parenthood is a major life event associated with changes in physiological and psychosocial functioning that can have a profound impact on mental health. Although research on this topic has traditionally focused on women, a small but growing number of studies have investigated the transition to parenthood in men. Men, like women, demonstrate an early and strong motivation to care for their infants/children and to form strong, rewarding attachments to them. Fatherhood can influence paternal mental health, and although it typically results in positive outcomes, it has been found to precipitate negative ones (i.e., postnatal depression and paternal psychosis). Further, the disruption of father-child interactions/attachments that results from paternal depression or loss of paternal custody after divorce has been consistently associated with decreased physical health and increased psychological distress in fathers. Indeed, paternal involvement in childcare has become increasingly recognized as equally important as maternal influences for child development and health as well as for the prevention and effective treatment of problem behaviors such as anxiety, attention- deficit/hyperactivity disorder (ADHD), substance use, and criminal behavior. Our knowledge about the neurobiology of parental behavior is almost exclusively derived from studies of maternal behavior, mainly because only ~3-5% of mammalian species display paternal behavior, and thus, an animal model has not yet been fully developed. In recent years, the socially monogamous prairie vole (Microtus ochrogaster) has emerged as an excellent animal model to study the neurobiology of complex social behaviors especially pair bonding behavior. As male prairie voles also display spontaneous paternal behavior and this behavior can be influenced by prior social experience with a female or by pharmacological manipulation of neurotransmitters including dopamine (DA), this animal model may provide an opportunity to study the neurobiology of paternal behavior. In this application, we will use male prairie voles as an animal model to test the hypothesis that the mesolimbic DA system regulates paternal behavior in a brain region-, receptor-, and behavior- specific manner. We will first compare paternal behaviors in male voles that have different social experiences with a female to establish correlations between variations of paternal behaviors and the level of DA marker expression in the brain. We will then examine changes of neuronal activation in DA-producing cells as well as changes in DA content, release, and receptor expression in selected brain areas during paternal behavior. Finally, we will pharmacologically manipulate DA receptors or the intracellular signaling cascades to reveal the functional role of central DA in paternal behavior. Together, data from these studies will shed light on the DA regulation of paternal behavior and firmly establish the prairie vole model for the study of paternal behavior. This, in turn, will facilitate the investigation of the neurobiology of paternal behavior - a scienific question that has been understudied despite its high translational value for human health. PUBLIC HEALTH RELEVANCE: The importance of father-child interactions and attachments for the health of the father is highlighted by studies indicating that their disruption - a common consequence of divorce due to loss of paternal custody - is consistently associated with decreased physical health, increased psychological distress, and an increased risk of suicide in fathers. Further, this disruption negatively impacts child development and the mother's physical and mental health. Here, we propose to use the socially monogamous prairie vole as an animal model to study the central dopamine regulation of male parental care, which will further our understanding of the neurobiological mechanism underlying paternal behavior.